The objectives of the proposed research are: (a) to investigate the role of cyclic AMP, cyclic GMP and various prostaglandins in the mechanism of bone resorption and apposition when teeth are subjected to orthodontic movement and when teeth are in the process of eruption and resorption; (b) to determine the effect of modulators of cyclic nucleotide levels, such as PTH, TCT, methyl xanthines and carbacol, on bone remodeling; (c) to determine the relationship between various prostaglandins and cyclic nucleotides as modulators of bone remodeling; and (d) to determine the effect of local applications of d.c. currents on alveolar bone remodeling and the concentration and distribution of cyclic nucleotides and prostaglandins. Quantitative methods for measuring bone concentration of cyclic AMP and microscopic localization of this cyclic nucleotide have been developed in our laboratory. Techniques for measurement of cyclic GMP and prostaglandins in bone extracts will be developed. The levels of these compounds will be measured in bone samples from areas surrounding erupting, resorbing and moving teeth. Utilizing immunohistochemical methods, cyclic nucleotides will be localized microscopically in bone and periodontal cells. Proving the hypothesis that prostaglandins and cyclic nucleotides play a significant role in bone remodeling will further elucidate our understanding of the mechanisms of tooth eruption, resorption, and movement, and will add significantly to our diagnostic and therapeutic ability.